CN114340523A

CN114340523A - Injector system for delivering medical implants

Info

Publication number: CN114340523A
Application number: CN202080061007.8A
Authority: CN
Inventors: J-M.布法特; K.范布塞尔
Original assignee: Novalon Ag
Current assignee: Novalon Ag
Priority date: 2019-08-26
Filing date: 2020-08-25
Publication date: 2022-04-12
Also published as: WO2021037860A1; PL4021319T3; EP4021319B1; AU2020338155A1; CA3148360A1; US20220280189A1; BE1027526A1; BE1027526B1; JP2022551041A; EP4021319A1; KR20220053581A

Abstract

An injector system (500) for injecting a non-deformable medical implant (200) into a subject by penetrating an organ, comprising: a holding element (100) having a proximal end (10) and a distal end (20) provided with a chamber (102) for accommodating an implant (200), wherein the holding element (100) is provided with an exit port (104) at the distal end (20) for slidable ejection of the implant (200) therethrough and into an aperture (404) of a needle part (402) of an injection needle assembly (400), a compliant member assembly (150) having a channel (154), comprising at least two compliant members (152), the compliant member assembly (150) having a biased state, wherein the at least two compliant members (152) additionally form a partial or total obstruction of the channel (154), wherein: the compliant member assembly (150) is configured in a biased state as a mechanical stop adapted to prevent the implant (200) from slidably entering the bore (404) under gravity, the channel (154) is configured to slidably receive the implant under an injection force, wherein at least two of the compliant members (152) deform and frictionally engage the implant (200), the compliant member assembly (150) is configured to align the implant with the bore of the needle component.

Description

Injector system for delivering medical implants

Technical Field

The present invention is in the field of syringe systems for medical implants, particularly for drug eluting medical implants.

Background

Injection of medical implants is typically performed by subcutaneous, intramuscular, or intradermal routes, and requires that the implant loaded into a syringe be advanced into the tissue of the patient along the bore of an injection needle. The implant may be any implant, such as a drug eluting implant, a radiopaque marker, encapsulated electronics. Where the implant is drug eluting, it typically elutes one or more active substances over an extended period of time, for example for delivery of LHRH agonists or antagonists (e.g. goserelin, leuprolide or buserelin), for treatment of hormone sensitive cancers such as breast or prostate cancer, or for treatment of benign gynaecological disorders (e.g. endometriosis, uterine fibroids and endometrial thinning).

The diameter of the implant needs to be carefully controlled; it determines the force required for injection. Adjusting the diameter of the implant is also critical for proper storage and transport. If the implant is larger than the prescribed dimensional tolerance, the injection force may be excessive and may cause damage to the implant. If the implant is smaller than the prescribed dimensional tolerance, the implant may fall out of the pre-filled syringe during shipping or during preparation by the administering physician. At the same time, it is desirable to minimize the diameter of the needle used to inject the implant. Larger diameter needles can cause more pain to the subject and in some cases require local anesthesia; it is desirable to avoid the administration of additional drugs (e.g., opiates). In addition, larger needle diameters increase wound and healing time. Furthermore, the ability to easily adapt syringes to different diameters and dosage implants would result in significant cost savings in manufacturing and seeking regulatory approval.

In US5772671, the implant is damaged by a plurality of friction ribs which prevent the implant from falling out, but which can damage the implant when it passes through (see fig. 7A to 10B herein). In US5201779, the device is used to inject a gel-like silicone implant through a nozzle into a surgical incision; such devices are not compatible with needles used to pierce organs (e.g., skin). In US2002/0188247, EP0639387, US2010/0331874, large diameter needles are employed in order to house the retaining spring mechanism within or as part of the needle itself, thereby increasing pain, trauma and healing time. In US2009/0270797, a spring mechanism is used to retain the needle within the body of the syringe, however, once the needle is advanced past the retaining mechanism, the implant falls out.

It is an object of the present invention to provide an injector system which overcomes the problems of the prior art and which maximizes the range of implants that can be delivered by the injector system.

Disclosure of Invention

Described herein is an injector system (500) for injecting a non-deformable medical implant (200) into a subject's body by penetrating an organ, comprising:

-a holding element (100) having a proximal end (10) and a distal end (20) provided with a chamber (102) for accommodating an implant (200),

-wherein the holding element (100) is provided at the distal end (20) with an outlet port (104) for slidable ejection of the implant (200) therethrough and into the bore (404) of the needle member (402) of the injection needle assembly (400),

-a compliant member assembly (150) having a channel (154), comprising at least two compliant members (152), the compliant member assembly (150) having a biased state, wherein the at least two compliant members (152) additionally form a partial or full obstruction of the channel (154), wherein:

-the compliant member assembly (150) is configured in a biased state as a mechanical stop adapted to prevent the implant (200) from slidably entering the bore (404) under gravity,

-the channel (154) is configured to slidably receive the implant under an injection force, wherein the at least two compliant members (152) deform and frictionally engage the implant (200),

-the compliant member assembly (150) is configured to align the implant with the bore of the needle component.

Described herein is an injector system (500) for injecting a medical implant (200) into a subject, comprising:

-wherein the holding element (100) is provided with an outlet port (104) at the distal end (20) for slidable ejection of the implant (200) therethrough,

a compliant member assembly (150) including at least one compliant member (152) configured to frictionally engage the implant (200) to resist passage therethrough, and

-wherein the implant (200) is slidable relative to the compliant member assembly (150).

The injector system (500) may further include an injection needle assembly (400) fluidly connected to the outlet port (104) of the holding element (100), the needle assembly (400) including a needle component (402) provided with an aperture (404) for passage of the implant (200), wherein the compliant member assembly (150) is configured to align the implant (200) to pass through the aperture (404). The number of compliant members (152) may be 2 or more. The compliant member assembly (150) may include 2, 3, or 4 compliant members (152) arranged in the compliant member assembly (150) to form a substantially circular profile. The compliant member assembly (150) may include an aperture defined by the compliant member (152), preferably by an inwardly directed edge of the compliant member (152), the aperture having a minimum width less than a minimum width of the transverse profile of the implant (200). The compliant member assembly (150) may be biased in a substantially planar configuration. The compliant member assembly (150) may be disposed within the retaining element (100) or, when an injection needle assembly (400) is present, within the needle assembly (400). The compliant member assembly (150) may also be configured as a compliant mechanical stop adapted to prevent the implant (200) from slidably entering the compliant member assembly (150) and passing through the exit port (104) under gravity. The injector system (500) may be configured such that the frictional engagement locks the position of the implant (200) relative to the compliant member assembly (150), wherein an injection force applied to the implant (200) of preferably less than 10N overcomes the locking. The syringe system (500) may also include a syringe (300) having a syringe barrel (320), wherein the retaining element (100) is disposed within the syringe barrel (320). The retaining element (100) may be a syringe barrel (320). The injector system (500) may further include an implant (200). The injector system (500) may be configured for subcutaneous, intramuscular, or intradermal injection of the implant (200). The syringe system (500) may further include a needle protection mechanism.

Drawings

Fig. 1A is a cross-sectional view of the injector system of the present invention with the compliant member resisting passage of the implant under gravity, thereby retaining the implant within the chamber of the retaining element.

Fig. 1B is a cross-sectional view of the injector system of the present invention with the compliant member assembly engaged with the implant to inhibit passage of the implant through the compliant member assembly to retain the implant within the chamber of the retaining element.

Fig. 2 shows a cross-sectional view of the syringe system of the present invention with the retaining element disposed within the barrel of the syringe.

Fig. 3 shows a cross-sectional view of the syringe system of the present invention wherein the retaining element is the barrel of the syringe.

Fig. 4 illustrates an injector system of the present invention comprising a retaining element and a needle assembly wherein the compliant member stop is part of the needle assembly.

Fig. 5 and 6 depict possible configurations of compliant member assemblies.

FIG. 7A is a photograph of an arrangement of rigid ribs each having a circular profile; fig. 7B is a schematic diagram of this configuration.

FIG. 8A is a photograph of an arrangement of rigid ribs each having a triangular profile; fig. 8B is a schematic diagram of this configuration.

FIG. 9A is a photograph of an arrangement of rigid ribs each having a rectangular profile; fig. 9B is a schematic diagram of this configuration.

FIG. 10A is a photograph of an arrangement of rigid ribs each having a triangular profile; fig. 10B is a schematic diagram of this configuration.

FIG. 11A is a photograph of a compliant member assembly according to the present invention; fig. 11B is a schematic diagram of this configuration.

Detailed Description

Before the present systems and methods are described, it is to be understood that this invention is not limited to the particular systems and methods or combinations described, as such systems and methods and combinations can, of course, vary. It is also to be understood that the terminology used herein is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.

As used herein, the singular forms "a", "an" and "the" include both singular and plural referents unless the context clearly dictates otherwise.

The term "comprising" or "comprises" as used herein is synonymous with "including" or "containing" and is inclusive or open-ended and does not exclude additional unrecited elements, components, or method steps. It is to be understood that the term "comprising" as used herein includes the term "consisting of.

The recitation of numerical ranges by endpoints includes all numbers and fractions subsumed within the respective range, as well as the recited endpoint.

As used herein, the term "about" or "approximately" when referring to measurable values such as parameters, amounts, durations, etc., is intended to include variations of +/-10% or less, preferably + 1-5% or less, more preferably +/-1% or less, still more preferably +/-0.1% or less of a particular value, provided such variations are suitable for practice in the disclosed invention. It is to be understood that the value to which the modifier "about" or "approximately" refers is itself also specifically and preferably disclosed.

Although the term "one or more" or "at least one", such as one or more of a group of elements or at least one of an element, is itself clear, by way of further example, the term includes reference to any one of the elements or any two or more of the elements, such as any 3, 4, 5, 6, 7, etc., of the elements and all of the elements.

All references cited in this specification are incorporated herein by reference in their entirety. In particular, the teachings of all references specifically mentioned herein are incorporated herein by reference.

Unless defined otherwise, all terms used in disclosing the present invention, including technical and scientific terms, have the meaning commonly understood by one of ordinary skill in the art to which this invention belongs. By way of further guidance, the term definitions are included to better understand the teachings of the present invention.

In the following paragraphs, the different aspects of the invention are defined in more detail. Each aspect so defined may be combined with any other aspect or aspects unless clearly indicated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature or features indicated as being preferred or advantageous.

Reference throughout this specification to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, the appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment, but may. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner, as will be apparent to one of ordinary skill in the art from this disclosure, in one or more embodiments. Moreover, although some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention and form different embodiments, as will be understood by those skilled in the art. For example, in the following claims, any of the claimed embodiments may be used in any combination.

In the description of the present invention, reference is made to the accompanying drawings which form a part hereof, and in which is shown by way of illustration specific embodiments in which the invention may be practiced. Parenthesized or bolded reference numerals attached to the respective elements are merely to illustrate the elements by way of example and are not intended to limit the respective elements. It is to be understood that other embodiments may be utilized and structural or logical changes may be made without departing from the scope of the present invention. The following detailed description is, therefore, not to be taken in a limiting sense, and the scope of the present invention is defined by the appended claims.

The terms "distal" and "proximal" are used in the specification and are terms commonly understood in the art as being toward (proximal) or away from (distal) the user (e.g., physician) side of the device. Thus, "proximal" means toward the user side, and thus away from the patient side. Conversely, "distal" means toward the patient side, and thus away from the user side.

The present invention relates to an injector system for injecting a medical implant. The syringe system includes a holding element having a proximal end and a distal end, the distal end being provided with a chamber for receiving the implant. The holding element is provided with an exit port at the distal end for slidable ejection of the implant. The injector system also includes a compliant member assembly including at least one compliant member configured to frictionally engage the implant to resist passage through or past the compliant member assembly. The compliant member assembly may also be configured to prevent the implant from entering therein under gravity, such as when the injector system is in transit. The compliant member assembly is disposed in a fixed relationship to the retaining element. Once engaged within the compliant member assembly, the implant can slide relative to the compliant member assembly. The present invention retains the implant in the retaining element during shipping and storage of the injection system. Furthermore, it maintains the integrity of the implant after injection. The compliant member allows the implant to remain intact as it passes through the compliant member assembly. Thus, the reliability of delivery (delivered dose and duration of release) is ensured.

The injection system is suitable for injecting an implant into a subject, preferably a mammal (e.g., an animal), preferably a human subject. In particular, it is suitable for subcutaneous, intramuscular or intradermal injection of implants.

The medical implant, also referred to herein as an implant, may be any implant suitable for injection. It is usually solid, i.e. neither liquid nor gas. It may be substantially incompressible or non-deformable. By non-deformable is meant that the implant retains its shape and size under the application of force, particularly the force experienced during injection. The implant may be sized for subcutaneous, intramuscular, or intradermal implantation. It preferably has a substantially cylindrical shape, although other shapes, for example shapes having an elliptical, C-shaped or polygonal profile, are also conceivable. It may have rounded or flat ends. It is preferably longitudinal. The longitudinal direction of the implant may be generally aligned with the longitudinal direction of the retaining element chamber and the needle aperture. It may be made of a biocompatible material. Medical implants have an overall contour that is a transverse cross-section, i.e. a cross-section perpendicular to the longitudinal axis of the implant. In case the medical implant is cylindrical, the overall contour is circular.

The implant may have one or more active pharmaceutical ingredients. The implant may be configured for slow release of one or more active pharmaceutical ingredients. The active pharmaceutical ingredient may be, for example, an LHRH agonist or antagonist. The active pharmaceutical ingredient may be buserelin, triptorelin, leuprorelin, goserelin, deslorelin, cisterlin, avorelin, nafarelin, lutrelin, a cysteine peptide, gonadorelin, disorelin, or luberlin. The implant may have a combination of one or more of the aforementioned active pharmaceutical ingredients. The implant may be biodegradable. The implant may be formed substantially of biodegradable polymeric materials such as poly (alpha-esters), polyurethanes, poly (ester amides), poly (orthoesters), polyanhydrides, polyphosphoesters.

The implant may include electronics. It may comprise one or more electronic sensors, one or more radio frequency transmitters, one or more radio frequency receivers. The electronic components may be encapsulated in a non-biodegradable polymeric material.

The implant may be radiopaque and act as a marker for medical imaging.

The holding element is provided with a chamber for accommodating the implant. The retaining element has a body, typically formed of a rigid material, such as polycarbonate or polypropylene, a styrenic polymer (ABS-acrylonitrile butadiene styrene), ABS, a cyclic olefin copolymer, polyethylene, or a polyolefin plastic. The body may be longitudinal. The body may be substantially cylindrical or frustoconical. The retaining element has a proximal end and a distal end. The retaining element has a chamber sized to receive the implant. The chamber is preferably sized to accommodate the entire implant. The chamber is preferably sized to accommodate the entire axial length of the implant. The chamber is used to store the implant so that the syringe system can be provided to the user ready for use. The retaining element may not form part of the needle assembly.

The retaining element may be disposed within the syringe barrel, for example as shown in fig. 2. The retaining element may be attached to the cartridge in a fixed relationship. The retaining element may be formed by a syringe barrel as shown in fig. 3. The syringe may be any type of syringe known in the art. For example a standard manual syringe, or an auto-injector such as described in WO 2014/174519. The syringe may include a needle protection mechanism to protect the needle after injection of the implant, as described for example in EP0966983 or EP1235603, which are well known in the art.

The distal end of the retaining element is provided with an exit port for passage of the implant. The outlet port is an opening in the body of the holding element, provided at the distal end, typically the distal terminal end. The exit port is configured for slidable ejection of the implant therethrough. Thus, the exit port is larger than the maximum profile of the implant. The outlet port may be smaller than a transverse cross-sectional profile of the holding element chamber. The system more preferably the retaining element is configured such that the outlet port can communicate with the needle assembly. In particular, the outlet port is aligned with the bore of the needle such that an implant passing through the outlet port enters the needle bore. The central axis of the outlet port may be coaxial with the central axis of the needle bore.

The retaining element may comprise a coupling for attachment to a needle assembly. With the retaining element contained within the barrel of the syringe, the syringe tip (e.g., 324 of fig. 2) is coupled with the needle assembly. Where the retaining element is the barrel of a syringe, the syringe tip (e.g., 324 of fig. 3) is coupled with the needle assembly.

The proximal end of the retaining element is provided with an inlet port for passage of a plunger deployment rod. The inlet port is an opening in the body of the holding element, provided at the proximal end, typically the proximal terminal end. The plunger deployment rod is slidable relative to the inlet port and moves the implant by applying an axial force. More specifically, the plunger deployment rod is configured to apply an axial force to the implant to eject from the chamber. The inlet port is larger than the maximum profile of the plunger deployment rod.

The needle assembly may be disposed at the distal end of the retaining element. The needle assembly is attached to or relative to the retaining element such that the implant, when deployed, can pass from the chamber and through the needle aperture. The attachment with respect to the retaining element may be a direct attachment or an indirect attachment, for example via one or more adapters. The needle assembly may be repeatedly detachable relative to the holding element. It may be substantially permanently attached relative to the retaining element. The transverse cross-section of the bore may be smaller than the transverse cross-section of the retaining element.

The needle assembly includes a needle member for penetrating an organ such as skin or muscle. The needle is a typical prior art syringe needle having a longitudinal shape, sharpened at one end for piercing the skin, and containing a bore connecting the distal end of the needle member to the proximal end of the needle member. When attached to the holding element, a connection is formed between the outlet port and the proximal end of the bore of the needle member. The needle hole is sized to accommodate passage of the implant. The needle is configured for subcutaneous, intramuscular, or intradermal routes of injection.

The needle assembly may further comprise a coupling member (e.g. a hub) for attaching the needle assembly to or relative to the holding element. Attached to or relative to the retaining element refers to direct attachment, or indirect attachment, such as via one or more adapters or via a syringe barrel in which the retaining element is placed (e.g., fig. 2 or 3). The coupling parts are typically push-fit connectors.

The system also includes a compliant member assembly including one or more compliant members configured to receive the implant. The compliant member assembly is configured for passage of an implant therethrough. The compliant member assembly has a channel connecting the distal side of the compliant member assembly to the proximal side thereof. The compliant member assembly (150) has a biased (rest) state in which at least two compliant members (152) additionally form a partial or full blockage of the channel. The compliant member assembly acts as a barrier between the chamber and the outlet port. It is configured to frictionally engage the implant to resist passage therethrough. The compliant member assembly at least partially retains the implant within the retaining element. The injector system preferably contains only one compliant member assembly.

The compliant member assembly is configured to frictionally engage the implant, thereby preventing passage therethrough. Preferably, the compliant member assembly frictionally engages the implant as the implant enters and passes through the channel under the injection force. By frictional engagement, it is meant that the compliant member assembly applies a frictional force to the implant, as shown, for example, in fig. 1B. The force is applied in a radial direction. By frictional engagement of the implant, each compliant member is deformed by axial movement and the size of the obstruction is reduced. When the implant is engaged with the compliant member, the latter acts as a stop to prevent passage of the implant relative to the compliant member assembly. By impeding is meant increasing the amount of force required to advance the implant compared to when not engaged. When engaged with one another, the interference preferably locks the position of the implant relative to the compliant member assembly, which can be overcome by a force greater than gravity, preferably by an injection force, i.e., a force applied axially to the implant. The injection force may be equal to or less than 10N, for example less than or equal to 6N. The injection force may be greater than 3N.

Typically, frictional engagement occurs during injection. The compliant member assembly is configured to retain the implant at least partially within the retaining element by applying a retaining or frictional force to the implant.

The compliant member may be further configured to conform to a mechanical stop or a mechanical stop. It prevents the implant from passing through the compliant member assembly under gravity. This stop function occurs during transport of the injector system containing the implant, typically when the implant is not engaged with the compliant member assembly, as shown, for example, in fig. 1A, and prevents the injector from falling out of the chamber. Thus, the compliant member assembly can be configured as a mechanical stop to retain the implant within the retaining element. Typically, the compliant members of the compliant member assembly are biased such that they at least partially occlude the outlet port of the retaining element. The implant may abut the compliant member assembly without engaging therewith. The mechanical stop function may be overcome by an axial force applied to the implant, for example, by a syringe plunger deployment rod. Engaging the implant with the compliant member assembly by applying sufficient force to the implant; the compliant member assembly applies a breaking force to the implant.

The compliant member assembly may be fixed relative to the retaining element (e.g., as shown in fig. 1) and/or the needle assembly (e.g., as shown in fig. 4). The compliant member assembly may be fixed relative to or attached to the wall of the holding element chamber. The compliant member assembly may be fixed distally relative to the needle aperture. The compliant member assembly may be fixed relative to or attached to an inner wall of a needle assembly coupling part (e.g., as shown in fig. 4).

The compliant member assembly can include at least one compliant member that is biased to block passage of the implant therethrough (e.g., fig. 5 and 6). The compliant member assembly may include at least two compliant members. As understood in the art, a compliant member is a member that can be deformed by the application of an external mechanical force, and returns to its original shape (biased or resting state) when the force is released. The compliant member may be a leaf spring. In the biased (rest) state (i.e., no force applied), the compliant member assembly can have a substantially planar configuration. The planar configuration may be perpendicular to a central axis of the syringe system, retaining element, or needle assembly coupling member. When the implant applies a force, the at least one compliant member yields and the distal end of the implant can be advanced through the compliant member to engage therewith. When engaged with one another, the force of the compliant member against the implant applies a braking frictional force to the implant, preventing it from passing through the compliant member.

The compliant member assembly may comprise 1, 2, 3 or 4 or more compliant members, preferably 2, 3 or 4 compliant members. Each compliant member may have a similar shape and/or size. Two or more compliant members may have similar shapes and/or sizes. One or more of the compliant members may have a different shape and/or size than the remaining compliant members. Each compliant member preferably projects radially (optionally perpendicularly ± 10 °) towards the central axis of the injector system, retaining element or needle assembly coupling part. Each compliant member protrudes vertically ± 10 ° relative to a central axis of the injector system, retaining element, or needle assembly coupling component. The compliant member may be arranged in the compliant member assembly to form a substantially circular profile, i.e., an outer shape. The compliant members may be circular or annular segments, preferably of the same size and shape, arranged in segments within a circular or annular ring. 1, 2, 3, or 4 or more compliant members in a biased state may additionally form a partial or full blockage of the channel. Additionally, this means that the size or footprint of each compliant member additionally combines to form a range of blockages. The compliant member assembly may include an aperture defined by the compliant member, preferably by an inwardly directed edge of the compliant member, having a minimum width (e.g., diameter) less than the minimum width (e.g., diameter) of the implant. The minimum width of the implant is measured in a transverse cross-section, i.e. a cross-section perpendicular to the longitudinal axis of the implant.

The compliant member may be attached to the retaining element, or the needle assembly, or the coupling component at the periphery of the circular or annular ring. The segmented compliant member may be attached to the wall of the holding element chamber at the circular or annular ring periphery, preferably towards the distal end, or to the wall of the needle aperture, or more preferably incorporated into a coupling part of the needle assembly.

The compliant member assembly may be configured to align the implant with the exit port or the bore of the needle component. For example, it may align the longitudinal axis of the implant substantially coaxially with the central axis of the outlet port. The compliant member assembly may be configured to align the implant with the bore of the needle. For example, it may align the longitudinal axis of the implant substantially coaxially with the longitudinal axis of the needle bore. For example, alignment may be achieved by providing a compliant member such that the force exerted by the compliant member acts on the implant in a net radial direction to align it with the longitudinal axis of the needle bore and/or the central axis of the outlet port. For example, the compliant members may be evenly arranged around the perimeter or circumference of the aperture, and/or radially or symmetrically opposed.

The compliant member may be made of any suitable compliant material, i.e., having inherent spring-like properties or may take the form of a spring-like material. Examples of suitable materials include polypropylene, silicone rubber, nitinol, Polyethylene (PE), thermoplastic elastomer (TPE), Polyacetal (POM).

Advantageously, the present invention improves the reliability of the syringe system, preventing unnecessary loss of the implant during storage or transport. It has been found that the use of a compliant member assembly does not increase the injection force required by the user compared to a standard syringe. The injection force reflects the amount of force required by the user to advance the implant through the holding element chamber and needle. In addition, the present invention reduces or prevents deformation of the implant. The compliant member allows the implant to remain intact as it passes through the compliant member assembly. Thus, the reliability of delivery (delivered dose and duration of release) is improved. The injector of the present invention reduces the injection force compared to non-compliant ribs and significantly reduces the injection force required for larger implant sizes.

By aligning the implant with the needle aperture, the compliant member assembly allows for a reduction in dimensional tolerances of the implant. In other words, the same syringe system can be used to manufacture implants with less stringent dimensional consistency, particularly in transverse cross-section. By moving the position of the retaining mechanism (compliant member assembly) out of the needle aperture, i.e., out of its distal end, the size of the needle can be reduced, thereby reducing trauma and pain during injection.

For some applications, the syringe system including the implant may need to be provided in a sterile state. The dimensions of the implant, particularly the dimensions of the transverse cross-section, may be altered (e.g., expanded or contracted in size) by the sterilization process. Because the injector system includes one or more compliant members, these dimensional changes of the implant can be accommodated without significantly increasing the injection force. Thus, an implant having an initial size will not fall out of the syringe system prior to sterilization and can still pass through a compliant member assembly that has expanded after sterilization. The method of sterilization may be any method, such as heat, gas technique or gamma radiation. Gamma radiation is preferred.

For other applications, depending on the length of time the active agent is released, different sizes of implant transverse profiles may be obtained; the same injector system can be used for different implant sizes, with similar centering and retaining functions, and without significantly increasing injection forces.

Fig. 1A and B show cross-sectional views of a holding element 100 of a syringe system 500 as described herein. The retaining element 100 has a truncated cone in which the chamber 102 is provided, said retaining element 100 having a proximal end 10 and a distal end 20. The chamber 102 holds a medical implant 200, typically for subcutaneous, intramuscular, and/or intradermal injection. An exit port 104 is at the distal end 20 of the retaining element 100 for passage of a medical implant during deployment. An access port 106 is provided at the proximal end 10 of the retaining element 100 for passage of a deployment rod (not shown). Compliant member assembly 150 is attached to the chamber 102 wall. The compliant member assembly 150 acts as a barrier between the chamber 102 and the outlet port 104. Compliant member assembly 150 has a partially plugged channel 154. In fig. 1A, the compliant member assembly 150 serves as a barrier to hold the implant 200 in the chamber 102 under gravity, particularly at the proximal end 10 of the compliant member assembly 150. In fig. 1B, implant 200 has been advanced in distal direction 20 and engaged with compliant member assembly 150, retaining it at least partially within chamber 102. The implant 200 passes through a portion of the passage 154, reducing the extent of occlusion.

Fig. 2 shows holding element 100 of fig. 1A and 1B disposed within barrel 320 of syringe 300. Syringe barrel 320 contains a holding chamber 322 for holding element 100. Syringe 300 further includes a plunger 360, plunger 360 including a shaft 362, a deployment rod 364, and a plunger head 366, and syringe barrel 320 terminating in a tip 324, tip 324 being a coupling for attachment to a needle assembly. Plunger 360 is in sliding engagement with syringe barrel 320, and a deployment rod 364 attached to distal end 20 of shaft 362 is configured to contact and advance implant 200 through the needle aperture. The distal end 20 of the barrel 320 is provided with a tip 324 for attachment to a needle assembly. The outlet port 104 of the retaining element 100 is aligned with the syringe tip 324 so that the implant 200 can pass through both and into the needle hole.

Fig. 3 shows holding element 100, which is barrel 320 of syringe 300. The syringe barrel 320 contains the chamber 102 for the implant 200. Syringe 300 further includes a plunger 360, plunger 360 having a shaft 362, a deployment rod 364, and a plunger head 366, and syringe barrel 320 terminating in a tip 324, tip 324 being a coupling for attachment to a needle assembly. Plunger 360 is in sliding engagement with syringe barrel 320, and a deployment rod 364 attached to distal end 20 of shaft 362 is configured to contact and advance implant 200 through the needle aperture. Compliant member assembly 150 is attached to the chamber 102 wall. Implant 200 has been advanced in distal direction 20 and engaged with compliant member assembly 150, retaining it at least partially within chamber 102. The distal end 20 of the barrel 320 is provided with a tip 324 for attachment to a needle assembly. The outlet port 104 of the retaining element 100 is aligned with the syringe tip 324 so that the implant 200 can pass through both and into the needle hole.

Fig. 4 shows a cross-sectional view of the retention element 100 coupled to a needle assembly 400 similar to that shown in fig. 1. The needle assembly 400 comprises a needle member 402 having a bore 404, which needle member 402 is attached at its proximal end 10 to the holding element 100 by means of a coupling member 406. The compliant member assembly 150 is disposed within the coupling component 406 at the distal end 20 of the outlet port 104.

Fig. 5 is a plan view of a compliant member assembly 150 that includes 4-segment leaflets that are compliant members 152 a-152 d arranged in diametrically opposed pairs, with an implant 200 engaged with the leaflets.

Fig. 6 is a plan view of a compliant member assembly 150 comprising 2 segments of leaflets, which are compliant members 152m through 152n arranged diametrically opposite one another, with an implant 200 engaged with the leaflets.

FIG. 7A is a photograph of an arrangement of four rigid ribs (450), each having a circular profile; fig. 7B is a schematic diagram of configuration (450').

FIG. 8A is a photograph of an arrangement of four rigid ribs (452), each having a triangular profile; fig. 8B is a schematic diagram of configuration (452').

Fig. 9A is a photograph of an arrangement of four rigid ribs (454), each having a rectangular profile; fig. 9B is a schematic diagram of configuration (454').

FIG. 10A is a photograph of an arrangement of two rigid ribs (456), each having a triangular profile; fig. 10B is a schematic diagram of configuration (456').

FIG. 11A is a photograph of a compliant member assembly according to the present invention including four compliant members 152 w-z; fig. 11B is a schematic view of the compliant member assembly of fig. 11A, with four compliant members (152w 'to z') indicated engaged with the implant 200.

Experiment of

Experiment 1

A syringe system for preparing a syringe for injecting an implant into a subject (e.g., subcutaneously, intramuscularly, or intradermally) includes a holding element contained within a syringe barrel, the holding element containing the implant, the system provided without a compliant member assembly. 11 such systems were prepared and each tested for implant injection efficacy in the trial. The length and diameter of the implant are comparable to each other and are suitable for placement in an injection system. Each implant is 1.3cm in length and each implant is 0.118cm in diameter. Each implant is made of a polymer containing an active pharmaceutical ingredient.

For each injector system without a compliant member assembly, the implant dropped out of the injector at the start of the trial or when the injector system was mounted on the test equipment. Three implants were lost in the trial. Of the remaining eight implants, seven have a diameter less than the lower tolerance limit and pass through the needle under gravity. The last remaining sample was at the minimum tolerance limit and fell out of the syringe upon contact with the shaft. Thus, the test protocol described in experiment 2 was not completed due to implant loss.

Experiment 2

A syringe system for preparing a syringe for injecting an implant into a subject (e.g., subcutaneously, intramuscularly, or intradermally) comprising a holding element contained within a syringe barrel, the holding element containing the implant, is provided without a compliant member assembly. The injector system is provided with one or more rigid ribs to prevent unwanted withdrawal of the implant. The rib is disposed in the needle assembly hub. Four different rib designs (a to D) were used, as shown in fig. 7 to 10, showing the rib profiles, respectively. The length and diameter of the implant are comparable to each other, suitable for placement in an injection system.

Each implant is 1.3cm in length and each implant is 0.118cm in diameter. Each implant is made of a polymer containing an active pharmaceutical ingredient. The length of each rib is 0.02 cm in the direction of the central axis of the needle. The ribs are arranged to contact the implant; the maximum channel diameter through the rib is less than the minimum diameter of the implant. Five such systems were prepared and the implant injection effect of each system was tested in the trial. The injection force was measured as follows: the injection system was placed upright with the needle facing down and placed on a testing machine equipped with a clamping mechanism to hold the injection system in a fixed position. The syringe is advanced at a speed of 100mm/min and the maximum force (force) exerted to fully eject the implant over time is measured. The results are given in table 1 below. The force required to damage the implant after injection, or to eject the implant, is very high.

Table 1, performance test results for 4 different designs of injector systems (a to D); five copies of each design (#1 to #5) were tested

Experiment 3

A syringe system for preparing a syringe for injecting an implant into a subject (e.g., subcutaneously, intramuscularly, and/or intradermally) comprising a holding element contained within a syringe barrel, the holding element containing the implant, is provided with a compliant member assembly of the present invention. The compliant member assembly is disposed in the needle assembly hub. Fig. 11A and 11B illustrate an exemplary design of a compliant member assembly. 120 copies of the syringe system were made, 60 of which were designed for implants having a first (smaller) size (size 1.3cm long, 0.118cm diameter) and 60 were designed for implants having a second (larger) size (size 1.8cm long, 0.147cm diameter). Each implant is made of a polymer containing an active pharmaceutical ingredient. The second size implant can be used to elute the active pharmaceutical ingredient over a longer time span. The implant injector systems for injecting the first and second size implants each have the same compliant member assembly. As shown in table 2, the effect of the implant injections of each syringe system was tested in the trial before and after sterilization by radiation. The injection force was measured as described above. The results are given in table 2 below.

Table 2, performance test results of 2 syringe systems with different sized implants before and after radiation sterilization.

Experiment 4

A syringe system for preparing a syringe for injecting an implant into a subject (e.g., subcutaneously, intramuscularly, and/or intradermally) comprising a holding element contained within a syringe barrel, the holding element containing the implant, is provided with a compliant member assembly of the present invention. The compliant member assembly is disposed in the needle assembly hub. Fig. 11A and 11B illustrate an exemplary design of a compliant member assembly. Sixty such systems were prepared and adapted to one target diameter implant. In each injector system, the implant is replaced by a calibrated rod made of steel, the diameter of which is at the lower diameter limit allowed for this particular injector system (0.110 cm). The effect of the implant injection of each syringe system was tested in trials before and after sterilization by radiation.

The injection force was measured as described above. The results are given in table 3 below.

Table 3, performance test results of a total of 60 syringe systems using a calibrated rod instead of an implant before and after radiation sterilization.

Claims

1. An injector system (500) for injecting a non-deformable medical implant (200) into a subject by penetrating an organ, the injector system (500) comprising:

-a compliant member assembly (150) having a through channel (154), comprising at least two compliant members (152), the compliant member assembly (150) having a biased state, wherein the at least two compliant members (152) additionally form a partial or full obstruction of the through channel (154), wherein:

-the through channel (154) is configured to slidably receive the implant under an injection force, wherein the at least two compliant members (152) deform and frictionally engage the implant (200),

2. The injector system (500) of claim 1, wherein the compliant member assembly (150) includes 2, 3, or 4 compliant members (152) arranged in the compliant member assembly (150) to form a substantially circular profile.

3. The injector system (500) according to claim 1 or 2, wherein the compliant member assembly (150) includes an aperture defined by the compliant member (152), preferably by an inwardly directed edge of the compliant member (152), the aperture having a minimum width that is less than a minimum width of the transverse profile of the implant (200).

4. The injector system (500) according to any one of claims 1 to 3, wherein the compliant member assembly (150) is biased in a substantially planar configuration.

5. The injector system (500) of any of claims 1-4, configured such that the frictional engagement locks a position of the implant (200) relative to the compliant member assembly (150), wherein an injection force applied to the implant (200) of preferably less than 10N overcomes the locking.

6. The syringe system (500) according to any of claims 1 to 5, further comprising a syringe (300) having a syringe barrel (320), wherein the retaining element (100) is disposed within the syringe barrel (320).

7. The syringe system (500) according to any one of claims 1 to 6, wherein the holding element (100) is a syringe barrel (320).

8. An injector system (500) according to any of claims 1-7, further comprising an injection needle assembly (400) in fluid connection with the outlet port (104) of the holding element (100), the needle assembly (400) comprising a needle member (402) for penetrating an organ of a subject, the needle member being provided with a hole (404) for passage of the implant (200), and further comprising a coupling member for attaching the needle member to the holding element (100) or relative to the holding element (100).

9. The injector system (500) of any of claims 1 to 8, wherein the compliant member assembly (150) is disposed within the retaining element (100) or within the needle assembly (400) coupling component (406).

10. The injector system (500) according to any one of claims 1 to 9, further comprising an implant (200).

11. The syringe system (500) according to any one of claims 1 to 10, configured for subcutaneous, intramuscular or intradermal injection of the implant (200).

12. The syringe system (500) according to any of claims 1 to 11, further comprising a needle protection mechanism.